Peeters Mariska Y M, Aarts Leon P H J, Boom Ferenc A, Bras Leo J, Tibboel Dick, Danhof Meindert, Knibbe Catherijne A J
Department of Clinical Pharmacy, St. Antonius Hospital, PO Box 2500, 3430 EM, Nieuwegein, The Netherlands.
Eur J Clin Pharmacol. 2008 Mar;64(3):329-34. doi: 10.1007/s00228-007-0399-9. Epub 2007 Nov 13.
To investigate the effect of cardiac output and liver blood flow on propofol concentrations in critically ill patients in the intensive care unit.
Five medical/surgical critically ill patients were enrolled in this preliminary study. Liver blood flow was measured using sorbitol. The cardiac output was measured by bolus thermodilution. NONMEM ver. V was applied for propofol pharmacokinetic analysis.
The clearance of propofol was positively influenced by the liver blood flow (P < 0.005), whereas no significant correlation between cardiac output and propofol clearance was found. A correlation between liver blood flow and cardiac output or cardiac index could not be assumed in this patient group.
Liver blood flow is a more predictive indicator than cardiac output for propofol clearance in critically ill patients when the techniques of hepatic sorbitol clearance and bolus thermodilution, respectively, are used. Further study is needed to determine the role played by liver blood flow and cardiac output on the pharmacokinetics of highly extracted drugs in order to reduce the observed high interindividual variabilities in response in critically ill patients.
探讨心输出量和肝血流量对重症监护病房危重病患者丙泊酚浓度的影响。
五名内科/外科危重病患者纳入本初步研究。使用山梨醇测量肝血流量。通过团注热稀释法测量心输出量。应用NONMEM V版进行丙泊酚药代动力学分析。
丙泊酚清除率受肝血流量的正向影响(P < 0.005),而未发现心输出量与丙泊酚清除率之间存在显著相关性。在该患者组中,无法假定肝血流量与心输出量或心脏指数之间存在相关性。
当分别采用肝山梨醇清除技术和团注热稀释法时,肝血流量比心输出量更能预测危重病患者丙泊酚的清除率。需要进一步研究以确定肝血流量和心输出量在高摄取药物药代动力学中所起的作用,从而减少危重病患者中观察到的个体间反应的高变异性。